Clinical profile, treatment selection, and early outcomes with TTR stabilizers to treat patients with transthyretin cardiac amyloidosis: a real-world study

Background

Transthyretin cardiac amyloidosis (ATTR-CM) is a progressive infiltrative cardiomyopathy treatable with transthyretin stabilizers (S-TTR): 1) tafamidis 61mg id, which is more broadly available and has long-term real-world data; and 2) acoramidis 712mg bid, restricted to an Early Access Program (EAP) in Portugal, with scarcer real-world evidence.

Objective

To characterize the real-world local experience with S-TTR to treat ATTR-CM, comparing baseline characteristics, treatment selection, safety, and clinical outcomes.

Methods

We conducted a retrospective, single-center cohort study of consecutive patients with ATTR-CM diagnosed according to the recommended algorithm. Treatment allocation reflected local protocols and EAP criteria. The primary endpoint was a composite of all-cause mortality or first cardiovascular hospitalization.

Results

A total of 180 patients received S-TTR: 170 were treated with tafamidis and 10 with acoramidis. The acoramidis group was slightly younger (80 [77-90] vs. 83 [79-83] years) and included more women (30% vs. 17%), with more pronounced renal dysfunction [creatinine clearance: 28 [25–33] vs. 44 [34–60] mL/min; p=0.001] and higher NT-proBNP levels (3954 [1372–13200] vs. 2197 [1323–4005] pg/mL; p=0.340). Echocardiographic parameters were similar between groups at baseline: interventricular septal thickness (17 [15–19] vs. 17 [14–21] mm), left ventricular ejection fraction (54% [43–58] vs. 53% [48–60]), tricuspid annular plane systolic excursion (17 [13–19] vs. 17 [13–20] mm) and Perugini grading (grade 3: 63% vs. 40%; grade 2: 35% vs. 40%).

Acoramidis was prescribed according to the EAP: 3 patients switched from tafamidis (1 due to worsening heart failure; 2 due to progressive renal dysfunction) and 7 initiated acoramidis upfront due to chronic kidney disease (glomerular filtration <25 mL/min). Patients received tafamidis and acoramidis for a median of 20 (10-35) vs. 3 (0-4) months (p<0.001). During follow-up, 45 patients (25%) met an event of the primary endpoint: 33 died and 25 had a first cardiovascular hospitalization (central figure). Thirty-month survival estimated by Kaplan–Meier for the overall cohort (n=180) was 81.7% (95% CI 75.8–87.6). The acoramidis cohort had a 100% event-free survival, with no new reported adverse events, although interpretation is limited by the short follow-up.

Conclusion

In this real-world cohort of patients with ATTR-CM treated with S-TTR, those on acoramidis had similar features compared to those on tafamidis, with the seldom exception of more pronounced renal impairment and higher NT-proBNP levels. Patients on acoramidis remained free of cardiovascular hospitalizations and mortality during follow-up. These early real-world findings support a favorable safety profile of acoramidis in EAP-selected patients unsuitable for or with disease progression while on tafamidis.

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